175TiP - A prospective phase II study to investigate the efficacy and safety of olaparib plus abiraterone and prednisone combination therapy in mHSPC patients with HRR gene mutation

Background

Homologous recombination repair (HRR) genes are a common type of mutation in advanced prostate cancer, approximately 10-15% of metastatic hormonal sensitive prostate cancer (mHSPC) patients harbor loss-of-function mutations in the HRR genes. Olaparib plus Abiraterone and Prednisone combination therapy has significantly prolonged radiographic progress free survival in metastatic castration-resistant prostate cancer patients with or without HRR mutation. The efficacy of combination therapy at mHSPC stage deserves further exploration.

Trial design

Olaparib plus Abiraterone and Prednisone are being evaluated in a single-center, single-arm, prospective phase II study in newly diagnosed mHSPC patients with HRR gene mutation, and a total of 30 subjects will be enrolled in Drum Tower Hospital, Nanjing, China. Eligible subjects will receive a regimen of oral Olaparib tablets 300 mg twice daily plus Abiraterone 1000mg and Prednisone 5mg once daily, until radiographic disease progression (as assessed by the investigator per RECIST 1.1 and PCWG 3) or intolerable adverse reactions (as judged by the local investigator per the actual clinical situation). The primary endpoint of the study is radiographic progression-free survival (rPFS). The secondary end points are prostate-specific antigen (PSA) response, PSA-PFS, objective response rate and safety. Key eligibility criteria include: (1) Have a qualifying HRR genetic mutation in tumor tissue as determined by the central laboratory for this study. Satisfactory HRR gene mutations are BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D and RAD54L mutations. (2) Both archival or new biopsies are acceptable. (3) Prior treatment with any new hormone agent or any taxane will be excluded. 1 of planned 30 patients have been enrolled until May. 2022.

Clinical trial identification

NCT05167175.

Legal entity responsible for the study

The authors.

Funding

AstraZeneca China.

Disclosure

All authors have declared no conflicts of interest.